Study of Lenvatinib in Subjects With Advanced Endometrial Cancer and Disease Progression

Inclusion criteria

• Histologically confirmed diagnosis of endometrial carcinoma.
• Radiographic evidence of disease progression according to modified RECIST 1.1 after 1 prior systemic, platinum-based chemotherapy regimen for recurrent metastatic or primary unresectable endometrial carcinoma for which no surgical or radiotherapy treatment option exists.
• Measureable disease meeting the following criteria:
• At least 1 lesion of greater than 1.0 cm in the longest diameter for a non-lymph node or greater than 1.5 cm in the short-axis diameter for a lymph node which is serially measureable according to modified RECIST 1.1 using computerized tomography / magnetic resonance imaging.
• Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency ablation must show evidence of progressive disease based on modified RECIST 1.1 to be deemed a target lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status less than 2.
• Adequate controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
• Adequate renal function defined as calculated creatinine clearance greater than 30 mL/min per the Cockcroft and Gault formula.
• Adequate bone marrow, blood coagulation, and liver functions, as defined in the study protocol.
• Negative serum or urine pregnancy test for women of reproductive potential.

Exclusion criteria

• Brain or leptomeningeal metastases, including stable metastases.
• More than 1 prior systemic chemotherapy regimen for recurrent metastatic or primary unresectable endometrial carcinoma or any treatment targeting vascular endothelial growth factor (VEGF)-directed angiogenesis. No restriction regarding prior adjuvant chemotherapy or hormonal therapy.
• Prior systemic anti-tumor therapy within 3 weeks.
• Not fully recovered from prior radiotherapy based on investigator judgement.
• Participants with greater than 1+ proteinuria on urine dipstick testing to undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with greater than 1 gm will be ineligible.
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association Class II; unstable angina; myocardial infarction or stroke within 6 months of the first dose of study drug; cardiac arrhythmia requiring medical treatment.
• Prolongation of QTc interval greater than 480 msec.
• Bleeding disorder or thrombotic disorders requiring anticoagulant therapy, such as warfarin, or similar agents requiring therapeutic INR monitoring (treatment with low molecular weight heparin [LMWH] allowed).
• Active hemoptysis within 3 weeks prior to the first dose of study drug.
• Females who are pregnant or breast feeding.